Voltage-gated sodium channel blockers

Abstract

The present invention relates to voltage-gated sodium channel blocker intermediates, compounds and dimers, corresponding pharmaceutical compositions, compound preparation and treatment methods for respiratory or respiratory tract diseases.

1 - 5 . (canceled) 
     
     
         6 . A compound of Formula (IV): 
       
         
           
           
               
               
           
         
       
       wherein:
 n is 0 or an integer from 1 to 5; 
 Y is straight or branched C 1-6  alkyl or cycloalkyl; 
 R 1  is H, halogen, straight or branched C 1-6  alkyl, phenyl, substituted phenyl, —NHR 1a , —SR 1b  or —OR 1c ; 
 R 3  is one or more substituents independently selected from —H, —OH, —CN, halogen, straight or branched C 1-6  alkyl, -straight or branched C 1-6  haloalkyl, -straight or branched C 1-6  alkoxy, -straight or branched C 1-6  alkoxy, —O(CH 2 ) x OR 1d , —C(O)R 1e , —C(O)OR 1f , —phenyl, —(CH 2 ) x -phenyl, —(CH 2 ) x -substituted phenyl, -phenyloxy, -substituted phenyloxy, —(CH 2 ) x -phenyloxy, —(CH 2 ) x -piperazinyl, —(CH 2 ) x -substituted piperazinyl, —(CH 2 ) x —N-substituted piperazinyl, —(CH 2 ) x NRC(O)-phenyl, —(CH 2 ) x NRC(O)-substituted phenyl, —O—(CH 2 ) x -phenyl, —O—(CH 2 ) x -substituted phenyl, —O(CH 2 ) x -1,4-benzodioxinyl, —O(CH 2 ) x -naphthalenyl, —O(CH 2 ) x -tetrazolyl, —S-phenyl, —S(CH 2 ) x phenyl, —SO 2 R 1g , —SO 2 N(R 1g ) 2 , —(CH 2 ) x —N(R 1h )—(CH 2 ) x R 1i ;
 wherein:
 R 1a , R 1b  or R 1c  as defined in R 1  above is phenyl or substituted phenyl; 
 R, R 1d , R 1e , R 1f , R 1g  or R 1h  as defined in R 3  is H, straight or branched C 1-6  alkyl; 
 R 1i  is phenyl, substituted phenyl, furanyl, substituted furanyl, thienyl, or substituted thienyl; 
 x as defined for substituents defined above is 0 or an integer from 1 to 5; 
 wherein:
 each substitutent as defined in R 3  above further is optionally substituted by one or more of following substituents selected from: —H, —OH, —CN, —NO 2 ,-halogen, —(CH 2 ) y —OH, —O(CH 2 ) y  CN, —OC(O)OH, —OC(O)R 1j , —C(O)OR 1k , —O(CH 2 ) y OR 1l ,-straight or branched C 1-6  alkyl,-straight or branched C 1-6  haloalkyl, -straight or branched C 1-6  straight or branched alkoxy, —NR 1m R 1n , —SO 2 R 1o , —S(CH 2 ) y R 1p , —NR 1q C(O)R 1r , aryl or heteroaryl; 
 wherein: 
 y as defined for variables above is 0 or an integer from 1 to 5, 
 R 1j , R 1k , R 1i , R 1m , R 1n , R 1o , R 1p , R 1q  or R 1r  is H, straight or branched C 1-6  alkyl, phenyl, substituted phenyl, pyridinyl, or substituted pyridinyl, —C(O)-phenyl, —C(O)substituted phenyl or (CH 2 ) x -2-oxo-1-pyrrolidinyl or (CH 2 ) x -2-oxo-N-pyrrolidinyl; or 
  wherein: 
  x is 0 or an integer from 1 to 5; 
  each phenyl or substituted phenyl substitutent as defined in R 1j , R 1k , R 1l , R 1m , R 1n , R 1o , R 1p , R 1q  or R 1r  above further is optionally substituted by one or more of following substituents selected from: 
 —H, —OH, —CN, —NO 2 ,-halogen, —(CH 2 ) y —OH, 
 —OC(O)OH, —OC(O)R 1s , —C(O)OR 1t , —SO 2 N(R 1u )—2-, straight or C 1-6  alkyl,-straight or branched C 1-6  haloalkyl, -straight or branched C 1-6  alkoxy; 
  wherein: 
  R 1s , R 1t , or R 1u  as defined above is H, straight or branched 
 C 1-6  alkyl, phenyl or substituted phenyl; or 
 
 
 
 
       a pharmaceutically acceptable salt thereof. 
     
     
         7 . A compound which is:
 1-methylethyl 2-[4-({3-[(2-thienylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,6-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3-chlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate; 1-methylethyl 2-{4-[(3-{[(2-chloro-4-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-methylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2-methylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-nitrophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2-chlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[3-(trifluoromethyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,4-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3-methylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-(ethyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridine carboxylate;   1-methylethyl 2-{4-[(3-{[(2-chloro-6-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-(acetyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridine carboxylate;   1-methylethyl 2-[4-({3-[(1,1,2,2-tetrafluoroethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(2-methylpropyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-(propyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridine carboxylate;   [(3-{[4-(3-{[(1-methylethyl)oxy]carbonyl}-2-pyridinyl)-1-piperazinyl]methyl}phenyl)oxy]acetic acid;   1-methylethyl 2-[4-({3-[(2-hydroxyethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({2-[(2-chloroethyl)oxy]ethyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-chlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-(phenylmethyl)-1-piperazinyl]-4-(phenyloxy)-3-pyridinecarboxylate;   1-methylethyl 4-[(2-fluorophenyl)amino]-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-[(3-chlorophenyl)amino]-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-[(4-cyanophenyl)amino]-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-{[2-(ethyloxy)phenyl]amino}-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-{[4-(1-methylethyl)phenyl]amino}-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-{[2-(1-methylethyl)phenyl]amino}-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-({3-[(ethyloxy)carbonyl]phenyl}amino)-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-[(2-ethylphenyl)amino]-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-{[4-(methyloxy)phenyl]amino}-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-(phenylamino)-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate; 1-methylethyl 2-[4-(phenylmethyl)-1-piperazinyl]-4-(phenylthio)-3-pyridinecarboxylate;   1-methylethyl 4-{[2-(methyloxy)phenyl]thio}-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate; 1-methylethyl 2-[4-({2-[(2-chlorophenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate; 1-methylethyl 2-{4-[(3-{[2-(trifluoromethyl)phenyl]amino}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[2-(methyloxy)phenyl]amino}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(2-methylphenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(2,6-difluorophenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(2-fluorophenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(2-chlorophenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({2-[(trifluoromethyl)oxy]phenyl}amino)phenyl)methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({3-(ethyloxy)carbonyl]phenyl}amino)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[2-fluoro-6-(trifluoromethyl)phenyl]amino}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(2,6-difluorophenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(2-fluorophenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(2-chlorophenyl)amino]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[4-(methyloxy)phenyl]amino}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-(2-furanylmethyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[2-(ethyloxy)phenyl]methyl}-1-piperazinyl)-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-[4-(2-thienylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-(3-furanylmethyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(5-methyl-2-thienyl)methyl]-1-piperazinyl}-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-(4-{[3-(phenyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-(4-{[3-(phenyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-[4-({3-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-[4-({3-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-(methyloxy)-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-(methyloxy)-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(2-cyanophenyl)methyl]-1-piperazinyl}-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-[4-({4-[(trifluoromethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-(4-{[4-(propyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[4-(2-methylphenyl)methyl]-1-piperazinyl}-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 4-phenyl-2-[4-({2-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-(methyloxy)-3-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-[4-(2-biphenylylmethyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[4-(3-fluoro-2-methylphenyl)methyl}-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-[(1-methylethyl)oxy]phenyl}methyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-[(1-methylethyl)oxy]phenyl}methyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2-chlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(4-fluorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-4-phenyl-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(ethyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[3-(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,6-difluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3,4-difluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3-chloro-4-fluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(1,1-dimethylethyl)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[({3-[(trifluoromethyl)oxy]phenyl}oxy)methyl]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2,3-bis(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2-chlorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[3,5-bis(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2-(trifluoromethyl)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3-cyanophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,4-dichlorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2-methylphenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-methylphenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-fluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-cyanophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(ethyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[3-(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,6-difluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3,4-difluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3-chloro-4-fluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(1,1-dimethylethyl)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2,3-bis(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2-chlorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[3,5-bis(methyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2-(trifluoromethyl)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3-cyanophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,4-dichlorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-methylphenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-fluorophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2-(ethyloxy)phenyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-cyanophenyl)oxy]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-[(4-{[ethyl(3-furanylmethyl)amino]methyl}phenyl)methyl]-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(ethyl{[3-(ethyloxy)phenyl]methyl}amino)methyl]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({ethyl[(5-methyl-2-thienyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(ethyl{[2-(ethyloxy)phenyl]methyl)amino}methyl]phenyl]methyl)-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(ethyl{[3-(methyloxy)phenyl]methyl}amino) methyl]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[ethyl(2-furanylmethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[ethyl(2-thienylmethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-[4-({4-[(methyloxy)carbonyl]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-[4-(phenylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[4-(methyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(2-cyanophenyl)methyl]-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-[4-(2-furanylmethyl)-1-piperazinyl]-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[4-(3-fluorophenyl)methyl]-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[3-(methyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-(3-furanylmethyl)-1-piperazinyl]-4-methyl-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-{4-[4-(5-methyl-2-thienyl)methyl}-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-cyanophenyl)methyl]-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-cyanophenyl)methyl]-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-cyano-4-fluorophenyl)methyl]-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(1,3-dimethyl-1H-pyrazol-4-yl)methyl]-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3,5-dimethyl-4-isoxazolypmethyl]-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-(acetylamino)phenyl]methyl}-1-piperazinyl)-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-(acetyloxy)phenyl]methyl}-1-piperazinyl)-4-methyl-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[1-(3-pyridinyl)-1H-pyrrol-2-yl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[4-(1H-tetrazol-5-yl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[4-(methylsulfonyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[2-[(cyanomethyl)oxy]-3-(methyloxy)phenyl]methyl}-1-piperazinyl)-4-methyl-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-[4-({1,2,5-trimethyl-4-[(methyloxy)carbonyl]-1H-pyrrol-3-yl]methyl)-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[2-(1-piperidinyl)-1,3-thiazol-5-yl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[2-(4-morpholinyl)-1,3-thiazol-5-yl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 4-methyl-2-(4-{[2-(4-methyl-1-piperazinyl)-1,3-thiazol-5-yl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({1-[3-cyano-4-(methyloxy)-2-pyridinyl]-1H-pyrrol-2-yl]methyl)-1-piperazinyl}-4-methyl-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[3-(trifluoromethyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3-bromophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-{[(2,4-dichlorophenyl)methyl]oxy}-3-(methyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3,5-bis(methyloxy)-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-(methyloxy)-3-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-{[(4-chlorophenyl)methyl]oxy}-3-(ethyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-{[(2-chlorophenyl)methyl]oxy}-3-(methyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-{[(2-chlorophenyl)methyl]oxy}-3-(ethyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-chloro-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-methyl-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2-chlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3,5-bis[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,4-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-{[(4-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-(ethyloxy)-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-(methyloxy)-2-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4,5-bis(methyloxy)-2-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3,5-dimethyl-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-hydroxy-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3,4-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-{[(2-chloro-6-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-{[(4-chlorophenyl)methyl]oxy}-3-(methyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-(methyloxy)-4-({[4-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-(methyloxy)-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-bromophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3,4-bis[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-(methyloxy)-4-[(phenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2-chloro-6-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(4-bromophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(3,5-dichlorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(4-methylphenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-(2-biphenylylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(3-chlorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-fluoro-3-(phenyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(4-chlorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-(9H-fluoren-2-ylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-(4-biphenylylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(4-methylphenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-(phenyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(3,4-dichlorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4′-methyl-3-biphenylyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-[(4-cyanophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4′-methyl-4-biphenylyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(4-fluorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(9-ethyl-9H-carbazol-3-yl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-(dibenzo[b,d]furan-4-ylmethyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(4-chlorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4′-chloro-3-biphenylyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(2-{[4-(methyloxy)phenyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(2,4-dichlorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[4-(methyloxy)phenyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-[(4-fluorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-[(4-chlorophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4′-[(methyloxy)carbonyl]-3-biphenylyl]methyl)-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4′-[(methyloxy)carbonyl]-4-biphenylyl]methyl)-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(4-cyanophenyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[4-(methyloxy)phenyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-(phenyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[4-(1,1-dimethylethyl)phenyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[2′-(trifluoromethyl)-3-biphenylyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({2-[(4-chlorophenyl)thio]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[2′-(trifluoromethyl)-4-biphenylyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3′-(methyloxy)-2-biphenylyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[3-(trifluoromethyl)phenyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[2-(phenyloxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[3,4-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(1,1-dimethylethyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[3,5-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,4,5-trifluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(2,3-dihydro-1,4-benzodioxin-5-ylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,6-difluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3,5-dimethylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[3-(dimethylamino)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,4-difluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,3-difluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(butyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(ethyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-ethylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2-fluoro-6-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(4-cyanophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,4-dimethylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-fluoro-3-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[(1-naphthalenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(methylsulfonyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(3,5-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[(2,3-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({3-[({4-[(methyloxy)carbonyl]phenyl}methyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-chloro-2-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[4-(1-methylethyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2,5-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2,4-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[3,4-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(1,1-dimethylethyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3-chlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[3,5-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,4,5-trifluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(2,3-dihydro-1,4-benzodioxin-5-ylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,6-difluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3,5-dimethyl phenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2-ethylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[3-(dimethylamino)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,4-difluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3-methylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3,4-difluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(butyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(ethyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-ethylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2-fluoro-6-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(5-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-cyanophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(4-methylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,6-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2-(ethyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,4-dimethylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-fluoro-3-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(1-naphthalenylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(methylsulfonyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(2-biphenylylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(3,5-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2,3-dichlorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[({4-[(methyloxy)carbonyl]phenyl}methyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-chloro-2-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(2-methylphenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[4-(1-methylethyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[4-({4-[(4-biphenylylmethyl)oxy]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2,5-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[3-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2,4-bis(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[2-(trifluoromethyl)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({4-[(2-chloro-6-fluorophenyl)methyl]-1-piperazinyl]methyl)phenyl}methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[4-(phenylmethyl)-1-piperazinyl]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate; 1-methylethyl 2-{4-[4-(4-{[4-(2-pyridinylmethyl)-1-piperazinyl]methyl}phenyl)methyl}-1-piperazinyl]-3-pyridinecarboxylate; 1-methylethyl 2-[4-({4-[(4-{[3-(methyloxy)phenyl]methyl}-1-piperazinyl)methyl]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate; 1-methylethyl 2-[4-({4-[(4-{[4-(methyloxy)phenyl]methyl}-1-piperazinyl)methyl]phenyl}methyl)-1-piperazinyl]-3-pyridinecarboxylate;   1-Methylethyl-2-{4-[(3-{[4-(methyloxy)phenyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridine carboxylate dihydrochloride;   1-Methylethyl-2-(4-{[Z-(trifluoromethyl)-3-biphenylyl]methyl}-1-piperazinyl)-3-pyridine carboxylate; 1-Methylethyl-2-(4-{[3-({[2-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate hydrochloride;   1-Methylethyl-2-(4-{[3-({[4-(ethyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-Methylethyl 2-[4-({4-[(ethylamino)methyl]phenyl}methyl)-1-piperazinyl]-3-pyridine carboxylate dihydrochloride;   1-Methylethyl 2-{4-[(4-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-[(4-{[[(2-Chloro-6-fluorophenyl)methyl](ethyl)ammonio]methyl}phenyl)methyl]-4-(3-{[(1-methylethyl)oxy]carbonyl}-2-pyridinyl)piperazin-1-ium di-maleate; 1-methylethyl 2-(4-{[4-({ethyl[(2-{[(1-methylethyl)oxy]carbonyl]phenyl)methyl]amino}methyl)phenyl}methyl}-1-piperazinyl)-3-pyridinecarboxylate dihydrochloride;   1-methylethyl 2-(4-{[4-({ethyl[(3-{[(1-methylethyl)oxy]carbonyl]phenyl)methyl]amino}methyl)phenyl}methyl}-1-piperazinyl)-3-pyridinecarboxylate dihydrochloride;   1-methylethyl 2-(4-{[4-({ethyl[(4-{[(1-methylethyl)oxy]carbonyl]phenyl)methyl]amino}methyl)phenyl}methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-[4-({2-[(dimethylamino)sulfonyl]phenyl}methyl)-1-piperazinyl]-3-pyridine carboxylate hydrochloride;   1-Methylethyl2-[4-({3-[(dimethylamino)sulfonyl]phenyl}methyl)-1-piperazinyl]-3-pyridine carboxylate;   1-methylethyl2-[4-({4-[(dimethylamino)sulfonyl]phenyl}methyl)-1-piperazinyl]-3-pyridine carboxylate;   1-methylethyl2-{4-[(4-{R{2-[(dimethylamino)sulfonyl]phenyl}methyl)(ethyl)amino)methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl2-{4-[(4-{R{3-[(dimethylamino)sulfonyl]phenyl}methyl)(ethyl)amino)methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate; 1-methylethyl2-{4-[(4-{R{4[(dimethylamino)sulfonyl]phenyl}methyl)(ethyl)amino)methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate; 1-Methylethyl 2-{4-[(4-{[[2-(2-chloro-6-fluorophenyl)ethyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate dihydrochloride;   1-methylethyl 2-{4-[(4-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate dihydrochloride hydrochloride; 1-methylethyl 2-(4-{[4-({ethyl[(3-fluorophenyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({ethyl[(4-fluorophenyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-{4-[(4-{[[(2,6-difluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate; 1-methylethyl 2-(4-{[4-({ethyl[(2-fluorophenyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate; 1-methylethyl2-{4-[(4-{[[(2,6-dichlorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate; 1-methylethyl 2-{4-[(4-{[[(3-chlorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate; 1-methylethyl2-{4-[4-(4-{[ethyl(phenylmethyl]amino}methyl)}phenyl)methyl]-1-piperazinyl)-3-pyridine carboxylate;   1-methylethyl2-{4-[(4-{[[(4-chlorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl2-{4-[(4-{[[(2-chlorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl2-(4-{[4-({ethyl[(6-methyl-2-pyridinyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-(4-{[4-({[(2-chloro-6-fluorophenyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-{4-[(4-{[[(2-chloro-6-fluorophenyl)carbonyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl2-(4-{[4-({[(2-chloro-6-fluorophenyl)methyl][3-(2-oxo-1-pyrrolidinyl)propyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-{4-[(3-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl2-(4-{[4-({ethyl[(2-methyl-3-pyridinyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-(4-{[4-({[(2-fluorophenyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-{4-[(2-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]; methyl]phenyl)methyl}-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl2-{4-[(4-{[[3-(2-chloro-6-fluorophenyl)propyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(phenylmethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}_-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({ethyl[(2-fluorophenyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate dihydrochloride;   1-methylethyl2-{4-[(4-{[ethyl(phenylmethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridine carboxylate dihydrochloride;   1-methylethyl2-(4-{[4-({[(2-chloro-6-fluorophenyl)carbonyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-(4-{[4-({ethyl[(6-methyl-2-pyridinyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridine carboxylate quaternary hydrochloride1-methylethyl2-(4-{[4-({[(2-fluorophenyl)carbonyl]amino}methyl)phenyl}methyl]-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(4-{[(phenylcarbonyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[4-({[(2-chloro-6-fluorophenyl)methyl]oxy}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl2-(4-{[4-({[(2-chloro-6-fluorophenyl)methyl]amino}methyl)phenyl]methyl}-1-piperazinyl)-3-pyridine carboxylate trihydrochloride; 1-methylethyl2-{4-[(4-{[[(2-chloro-6-fluorophenyl)carbonyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate dihydrochloride; or   a pharmaceutically acceptable salt thereof.   
     
     
         8 . A compound which is:
 1-methylethyl 2-{4-[(4-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   bis(1-methylethyl) 2,2′-{benzene-1,4-diylbis[methanediyl(ethylimino)(3S)-3,1-pyrrolidinediyl]}(3-pyridinecarboxylate);   benzene-1,4-diylbis[methanediyl(ethylimino)(3R)-3,1-pyrrolidinediyl-2,3-pyridinediylmethanediyl]bis(3,3-dimethylbutanoate; 1-methylethyl 2-{4-[(3-{[(2-chloro-6-fluorophenyl)methyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-{4-[(3-{[4-(methyloxy)phenyl]oxy}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[Z-(trifluoromethyl)-3-biphenylyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[2-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-[(4-{[[(2-Chloro-6-fluorophenyl)methyl](ethyl)ammonio]methyl}phenyl)methyl]-4-(3-{[(1-methylethyl)oxy]carbonyl}-2-pyridinyl)piperazin-1-ium di-maleate; 1-methylethyl 2-(4-{[3-({[4-(ethyloxy)phenyl]methyl}oxy)phenyl}methyl]-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-[(3R)-3-(ethyl{[4-({ethyl[(3R)-1-(1-{2-[(1-methylethyl)oxy]-2-oxoethyl]ethenyl)-3-pyrrolidinyl]amino}methyl)phenyl}methyl}amino)-1-pyrrolidinyl]-3-pyridinecarboxylate;   1-methylethyl 2-(4-{[3-({[3-(methyloxy)phenyl]methyl}oxy)phenyl]methyl}-1-piperazinyl)-3-pyridinecarboxylate;   1-methylethyl 2-{(3R)-3-[ethyl({2-[(phenylmethyl)oxy]phenyl}methyl)amino]-1-pyrrolidinyl}-3-pyridinecarboxylate; bis(1-methylethyl) 2,2′-{benzene-1,4-diylbis[methanediyl(2S)-1,2-pyrrolidinediylmethanediyloxy]}di(3-pyridinecarboxylate); or   
       pharmaceutically acceptable salts thereof. 
     
     
         9 . A compound which is 1-Methylethyl 2-{4-[(4-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate 
       
         
           
           
               
               
           
         
       
       or 
       a pharmaceutically acceptable salt thereof. 
     
     
         10 . A compound which is 1-Methylethyl 2-{4-[(4-{[[(2-chloro-6-fluorophenyl)methyl](ethyl)amino]methyl}phenyl)methyl]-1-piperazinyl}-3-pyridinecarboxylate 
       
         
           
           
               
               
           
         
       
     
     
         11 . A compound which is 1-[(4-{[[(2-Chloro-6-fluorophenyl)methyl](ethyl) ammonio]methyl}phenyl)methyl]-4-(3-{[(1-methylethyl)oxy]carbonyl}-2-pyridinyl)piperazin-1-ium di-maleate 
       
         
           
           
               
               
           
         
       
     
     
         12 - 29 . (canceled) 
     
     
         30 . A pharmaceutical composition, which comprises a compound according to  claim 6  or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable adjuvant, excipient or carrier. 
     
     
         31 . A pharmaceutical composition, which comprises a compound according to  claim 9  or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable adjuvant, excipient or carrier. 
     
     
         32 . A pharmaceutical composition, which comprises a compound or a pharmaceutically acceptable salt thereof according to  claim 11  and at least one pharmaceutically acceptable adjuvant, excipient or carrier. 
     
     
         33 . A method for treatment of respiratory or respiratory tract diseases, which comprises administering an effective amount of a compound according to  claim 6  to a subject in need thereof. 
     
     
         34 . (canceled) 
     
     
         35 . A method for treatment of respiratory or respiratory tract diseases, which comprises administering an effective amount of a pharmaceutical composition according to  claim 31  to a subject in need thereof. 
     
     
         36 . The method according to  claim 35 , wherein the respiratory or respiratory tract diseases are selected from asthma, allergen-induced asthmatic reactions, cystic fibrosis, bronchitis, chronic bronchitis, chronic obstructive pulmonary disease (COPD), cough, adult respiratory distress syndrome (ARDS), chronic pulmonary inflammation, rhinitis and upper respiratory tract inflammatory disorders (URID), ventilator induced lung injury, silicosis, pulmonary sarcoidosis, idiopathic pulmonary fibrosis or bronchopulmonary dysplasia. 
     
     
         37 . A method for treatment of chronic obstructive pulmonary diseases (COPD), which comprises administering an effective amount of a compound according to  claim 6  to a subject in need thereof. 
     
     
         38 . A method for treatment of chronic obstructive pulmonary diseases (COPD), which comprises administering an effective amount of a pharmaceutical composition according to  claim 30  to a subject in need thereof. 
     
     
         39 . A method for treatment of cough, which comprises administering an effective amount of a compound according to  claim 6  to a subject in need thereof. 
     
     
         40 . A method for treatment of cough, which comprises administering an effective amount of a pharmaceutical composition according to  claim 30  to a subject in need thereof. 
     
     
         41 - 44 . (canceled) 
     
     
         45 . A method for treatment of chronic obstructive pulmonary diseases (COPD), which comprises administering an effective amount of a compound according to  claim 9  to a subject in need thereof. 
     
     
         46 . A method for treatment of chronic obstructive pulmonary diseases (COPD), which comprises administering an effective amount of a compound according to  claim 11  to a subject in need thereof. 
     
     
         47 . A method for treatment of chronic obstructive pulmonary diseases (COPD), which comprises administering an effective amount of a pharmaceutical composition according to  claim 31  to a subject in need thereof. 
     
     
         48 . A method for treatment of cough, which comprises administering an effective amount of a compound according to  claim 9  to a subject in need thereof. 
     
     
         49 . The method for treatment of cough according to  claim 49 , wherein the cough is dry cough, wet cough, croupy cough or chest cough. 
     
     
         50 . A method for treatment of cough, which comprises administering an effective amount of a pharmaceutical composition according to  claim 31  to a subject in need thereof. 
     
     
         51 . The method for treatment of cough according to  claim 51 , wherein the cough is dry cough, wet cough, croupy cough or chest cough.